Current evidence indicates that surgical bypass of large segments of the small intestine in morbidly obese humans effectively produces weight loss and reverses hypertensive, diabetic, and hyperlipidemic disorders and improves socioeconomic disability. Small intestinal bypass in morbidly obese individuals is associated with significant increases in fatty infiltration of the liver during the first year following the operation in 95% of the patients and 2% to 5% will have clinical liver failure. While the other adverse sequelae of the operation can be effectively controlled, possible death from liver failure is a deterrent to bypassing the small bowel of the morbidly obese patient. The principal investigator has developed and evaluated an obese rat model for the study of hepatic changes following small intestinal bypass. These studies have demonstrated that the obese rat serves as an adequate model closely reproducing the chemical and morphological changes occurring in the obese human before and after small intestinal bypass. The proposed research will utilize the rat model to investigate the biochemical factors producing the hepatic steatosis. Prevention of steatosis will be attempted by antibiotic therapy, selective nutritional supplementation, and elimination of a period of starvation by intravenous nutritional supplementation. We will evaluate the lifelong effects of the operation in the rat model by performing longevity studies following intestinal bypass. It is anticipated that the proposed research will produce information concerning the etiology of steatosis following small intestinal bypass and develop techniques to prevent its occurrence.